This is an Open Access article distributed under the terms of the Creative Commons Attribution License (
http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The application of laparoscopic surgery for advanced gastric cancer (AGC) remains
questionable on account of technical difficulty of D2 lymphadenectomy, and there has
been few large-scale follow-up results regarding the oncological adequacy of laparoscopic
surgery compared with that of open surgeries for AGC. The aim of this study is to
evaluate technical feasibility and oncological efficacy of laparoscopy-assisted gastrectomy
(LAG) for advanced gastric cancer without serosal invasion.

Methods

From January 2008 to December 2012, 1114 patients with gastric cancer underwent D2
gastrectomy, including 336 T2 and T3 patients in term of depth of invasion. Of all
336 patients, 224 underwent LAG, while open gastrectomy (OG) performed on the other
112 patients. The comparison was based on the clinicopathologic characteristics, surgical
outcome, and follow-up results.

Results

There are not significant differences in clinicopathological characteristics between
the two groups (P > 0.05). The operation time and first ambulation time was similar
in the two groups. However, estimated blood loss, bowel function recovery time and
duration of hospital stay were significantly less in the LAG group. No significant
difference in morbidity and mortality was found between the LAG group and OG group
(11.1% vs. 15.3%, P = 0.266; 0.9% vs. 1.8%, P = 0.859). The mean number of resected
lymph nodes (LNS) between the LAG group and OG group was similar (30.6 ± 10.1 vs.
30.3 ± 8.6, P = 0.786). Furthermore, the mean number of removed LNS in each station
was not significantly different in the distal gastrectomy and total gastrectomy (P > 0.05).
No statistical difference was seen in 1 year survival rate (91.5% vs. 89.8% P > 0.05)
and the survival curve after surgery between the LAG group and OG group.

Conclusion

Laparoscopy-assisted D2 radical gastrectomy is feasible, effective and has comparative
oncological efficacy compared with open gastrectomy for advanced gastric cancer without
serosal invasion.

Keywords:

Background

Since laparoscopy-assisted gastrectomy (LAG) for early gastric cancer was initially
reported in 1994
[1], it has been increasingly used to treat early gastric cancer as it is less invasive
than conventional open gastrectomy (OG)
[2,3]. However, its wider acceptance as an alternative to the open approach remains contentious.
The reasons for slow acceptance of this procedure include concerns about safety and
doubts about the effectiveness of lymphadenectomy compared to conventional open gastrectomy.
This study compared the clinical features of 224 patients who underwent LAG with 112
patients who underwent OG with D2 lymph node dissection, for pathologically confirmed
stage T2-3 gastric carcinoma. The aim of this study was to evaluate the feasibility
and short-term outcome of LAG for advanced gastric cancer (AGC) without serosal exposure.

Methods

Materials

From January 2008 to December 2010, 1,114 patients diagnosed with primary gastric
cancer were treated with curative resection (R0) at the department of Gastric Surgery,
Fujian Medical University Union Hospital, Fuzhou, China. Of these patients, 336 had
pathologically confirmed stage T2 (depth of invasion in submucosa) or T3 (depth of
invasion in muscularis propria) cancer according to the 7th edition of the Union for
International Cancer Control (UICC)
[4]; of the 336 patients, 224 underwent LAG, and 112 patients underwent OG. Selection
of laparoscopic versus the open approach for patients diagnosed preoperatively with
AGC was by patient choice.

Nodal material was separately dissected from the enbloc specimen at the end of the
procedure by the surgeons, and the remaining nodes were identified and retrieved by
specialized pathologists from formalin-fixed surgical specimens without using any
specific technique to increase nodal retrieval rate. The lymph nodes of the stomach
are defined and given station numbers according to the 3rd English edition of Japanese
classification of gastric carcinoma
[5]. Staging was done according to the 7th edition of the UICC tumor, mode, metastasis
(TNM) classification
[4]. Postoperative complications have been classified using the therapy-oriented severity
grading system (TOSGS) as follows: grade 1, no need for specific intervention; grade
2, need for drug therapy such as antibiotics; grade 3, need for invasive therapy;
grade 4, organ dysfunction with ICU stay; grade 5, death. This type of system is applied
in medical oncology and has resulted in the National Cancer Institute’s uniform system
of complication reporting.

All procedures were performed after obtaining informed consent following the explanation
of the surgical and oncologic risks. Inclusion criteria were as follows: histologically
confirmed adenocarcinoma of the stomach; pathologically confirmed stage T2-T3; no
evidence of distant metastasis by means of abdominal computed tomography(CT) and/or
abdominal ultrasound and posteroanteriorchest radiograph; D2 lymphadenectomy with
curative R0 according to pathological diagnosis after the operation. Exclusion criteria
were as follows: intraoperative evidence of peritoneal disseminated or distant metastasis;
incomplete of pathological data; diagnosis of positive serosal invasion during the
operation. Follow-up was carried out by trained investigators through mailings, telephone
calls, visits to patients or recording of the patients’ consultations at the outpatient
service every 6 months. The survival time was the time from the surgical intervention
until the last contact, the date of death, or the date that the survival information
was collected.

Surgical procedure

The D2 lymphadenectomy was always performed according to the lymph node classification
of the Japanese Gastric Cancer Association
[5]. All operations were performed under general anesthesia. Patients were placed in
the supine position, with legs apart and 20 to 30° head-up tilt. The surgeon stood
on the left of the patient, the assistant surgeon stood on patient’s right, and the
videolaparoscope operator stood between the patient’s legs. Five trocars were used;
one 10-mm trocar for the laparoscope was inserted below the umbilicus. One 12-mm trocar
was inserted in the left pre-axillary line 2 cm below the costal margin as a major
hand port. A 5-mm trocar was placed at the contralateral site for traction and exposure
of the liver. A 5-mm trocar was inserted as an accessory port in the left and right
mid clavicular line 2 cm above the level of the umbilicus.

Laparoscopic total gastrectomy

The stomach and the peritoneal cavity were inspected to rule out adjacent organ invasion
and peritoneal seeding using a 30° forward oblique laparoscope. Then under pneumoperitoneum
of 12 to 15 mmHg, the gastrocolic ligament was divided using ultrasonic-activated
scissors along the border of the transverse colon, thus including the greater omentum
in the specimen to be resected. The dissection moved to the hepatic flexure and the
pylorus. Then the superior leaf of the mesocolon was dissected. After the right gastroepiploic
vein was exposed and divided with double clips, the right gastroepiploic artery was
vascularized and cut with titanium clips at its origin from the gastroduodenal artery,
just above the pancreatic head, to dissect Group 6 (Figure
1). The stomach was lifted upwards (towards the head)to expose the gastropancreatic
fold. The left gastric vein was carefully prepared and separately divided at the upper
border of the pancreatic body and then the left gastric artery was vascularized to
remove Group 7. The lymph nodes along the proximal splenic artery (Group 11p) were
removed. Subsequently, the dissection was continued to the right along the artery
to remove the nodes along the celiac axis and the common hepatic artery (Group 9,
8a). The right gastric artery was then exposed and divided at its origin with double
clips, thus creating room for the dissection of the suprapyloric lymph nodes (Group
5). Along the border of the liver, the lesser omentum was dissected and the lymph
nodes of the anterior region of the hepatoduodenal ligament (Group 12a) were dissected
and removed (Figure
2). The dissection was continued toward the distal pancreas to uncover the distal splenic
artery and splenic vein, then the fatty connective tissue, including the lymph nodes
along the distal splenic artery (Group 11d) and the lymph nodes around splenic hilum
(Group 10), were completely removed. The left gastroepiploic artery, posterior gastric
artery, and all short gastric vessels were divided with either harmonic scissors or
clips, and the lymph nodes were removed (Group 4sa, 4sb) (Figure
3). Before gastric transection, the cardiac nodes were dissected enbloc including the
right cardiac (Group 1) and left cardiac nodes (Group 2). After dissection of the
gastric and gastroepiploic vessels, the phrenoesophageal membrane and vagal nerve
were divided.

Laparoscopic distal gastrectomy

All steps were performed as in the total gastrectomy procedure but without the mobilization
of the distal esophagus, gastric fundus and Group10, 11d and some Group 4sa lymph
nodes. The stomach proximal transection site was selected according to the location
of the tumor and the procedure was performed with a linear stapler.

After the laparoscopic operation, a small laparotomy incision was made under the xyphoid
(5 to 7 cm). Distal gastrectomy with Billroth I, Billroth II or total gastrectomy
with Roux-en-Y anastomosis were extra corporeally performed using the hand-sewn method.
The specimen was pulled out of the peritoneal cavity through the small laparotomy
incision. OG was performed using the same methods as LAG. The region of lymphadenectomy
in OG was mostly the same as that for LAG.

Statistical analysis

All statistical analyses were conducted using the statistical program SPSS 18.0. The
data were collected and expressed as mean ± SD. A statistical analysis was performed
using the chi-square test, or the unpaired Student’s t-test as appropriate. Survival was evaluated using the Kaplan-Meier method, including
the log-rank test for model. P < 0.05 was considered statistically significant.

Results

Patient clinicopathologic characteristics

The clinicopathologic characteristics of the patients are presented in Table
1. The series included 72 men and 264 women, with a mean age of 61.3 years (range 32
to 89 years). The age, gender, resection extent, tumor depth, tumor size, body mass
index (BMI), location of neoplasm, gross type, histologic type, American Society of
Anesthesiologists(ASA) score, comorbidity, lymph node status (N stage), TNM stage
and gastrointestinal reconstruction type did not differ between the LAG group and
OG group (P > 0.05).

Intraoperative and postoperative characteristics

The operation time and first ambulation time did not differ between the LAG group
and OG group. However, estimated blood loss, transfusion amounts, bowel function recovery
time and duration of hospital stay were significantly lower in the LAG group(P < 0.05) (Table
2).

Morbidity and mortality

The overall postoperative morbidity and mortality rates among all patients were 12.5%
and 1.2%, respectively. The postoperative complications were not different between
the LAG and OG groups (11.1% vs. 15.3%, P = 0.266), and we also observed no difference between the two groups using TOSGS.
The mortality rate in the LAG group was 0.9% compared with 1.8% in the OG group, but
the difference was not statistically significant (P = 0.859) (Table
3).

Dissection of lymph nodes

The mean number of harvested lymph nodes was 30.5 ± 9.6 in all patients with a median
of 29 (range 10 to 64). The mean number of retrieved lymph nodes was not different
between the two groups (30.6 ± 10.1 in the LAG group vs. 30.3 ± 8.6 in the OG group)
(P = 0.786). Furthermore, the mean number of removed lymph nodes in each station was
not significantly different in distal gastrectomy or total gastrectomy (P > 0.05) (Figure
4,
5).

Figure 4.Distribution of harvested perigastric lymph nodes in the laparoscopy-assisted distal gastrectomy(LADG)and the open distal gastrectomy(ODG)groups. The mean number of removed lymph nodes in each station was not significantly difference
between the two groups (P > 0.05).

Figure 5.Distribution of harvested perigastric lymph nodes laparoscopy-assisted total gastrectomy(LATG)and the open total gastrectomy(OTG)groups. The mean number of removed lymph nodes in each station was not significantly different
between the two groups. (P > 0.05).

Survival time

The follow-up rate was 98.9% (316 patients). Of these, the LAG follow-up rate was
94.6% (212 patients) and the OG follow-up rate was 92.9% (104 patients). The median
follow-up period was 19 months (range 1 to 48 months). The respective 1-year survival
rates were 91.5% (LAG) and 89.8% (OG).There was no significant differences in the
overall survival curve between the two groups (Figure
6) (P = 0.297).

Figure 6.Overall survival curves for patients in the laparoscopy-assisted and the open gastrectomy groups. There were no significant differences in overall survival curve between the two groups
(P = 0.297).

Discussion

LAG shares obvious advantages of being minimally invasive and has the same short-
and long-term efficacy compared with traditional open surgery in the treatment of
early gastric cancer
[6-9].Therefore, it has gradually become acknowledged by counterpart clinicians. Since
2002, the Japanese gastric cancer treatment guidelines have recommended laparoscopy-assisted
gastrectomy as the standard procedure for early gastric carcinoma.

As experience with LAG for early gastric cancer has substantially increased, some
surgeons have become concerned about laparoscopic surgery for AGC
[10-14]. Ninety percent of patients diagnosed with gastric carcinoma in China have advanced-stage
disease. The study of laparoscopic techniques in AGC would seem sensible Current evidence
is compatible with D2 lymph node dissection as the preferred treatment for fit patients
with AGC, in centers that can demonstrate low operative mortality
[15,16]. Furthermore, the Japanese gastric cancer treatment guidelines have adopted D2 lymph
node dissection as the standard technique for AGC. However, the application of laparoscopic
surgery for AGC remains questionable on account of the technical difficulty of D2
lymphadenectomy, and there has been few large-scale follow-up data on the oncologic
adequacy of laparoscopic surgery compared with that of open surgery for AGC. Nevertheless,
some small case-studies also showed that laparoscopic D2 lymphadenectomy is a safe
procedure for AGC if the surgery is performed by experienced surgeons
[13,17,18]. The Japanese gastric cancer treatment guidelines regard LAG as an investigational
treatment
[19]. Some scholars
[20-22] studying the laparoscopic learning curve have found that once surgeons span the learning
curve reaching a plateau phase, the superiority of laparoscopic gastric carcinoma
surgery will gradually appear more often compared with open surgery.

We have been performing LAG for gastric cancer since 2007. In the present study, we
selected patients treated after January 2008, by which time we had overcome the learning
curve having performed approximately 300 laparoscopic D2 gastrectomy procedures for
gastric cancer, to reduce the influence of lack of surgical experience on the results.
In this study, we compared 224 patients who underwent LAG with 112 who underwent OG
for AGC without serosal exposure, in the same period. The data show that the LAG and
OG groups shared similar operating times and first ambulation times, while the LAG
group had less intraoperative blood loss, earlier recovery time for bowel movement,
and a shorter postoperative stay in hospital. LAG was also shown to have obvious advantages
of being minimally invasive for treatment of AGC without invasion of serosa.

The incidence of postoperative morbidity and mortality in the LAG group in the present
study was similar to that of other reports. Although no significant difference in
postoperative morbidity or mortality was observed between the LAG and OG groups (11.1%
vs. 15.3%, and 0.9% vs. 1.8%, respectively, P > 0.05),our results show that LAG for AGC has similar intraoperative and postoperative
complications to open surgery, and may even be better than OG. LAG D2 radical lymphadenectomy
is a safe technique with fast postoperative recovery in the treatment of AGC without
invasion of serosa. Therefore, LAG for AGC may be acceptable from this viewpoint.

The advantages of minimally invasive laparoscopic surgery have gradually been recognized,
but laparoscopic D2 lymph node dissection is difficult to handle due to the complicated
vessels, numerous anatomical layers and the complex lymph node metastasis pathway
around the stomach. Therefore, many scholars still doubt whether LAG can achieve as
considerable a radical effect as open surgery. Sato
[23] compared 36 cases of laparoscopy-assisted D2 lymph node dissection and 130 cases
of open surgery for AGC. The average number of retrieved lymph node in the laparoscopic
and open surgery group was (32 ± 12) and (35 ± 1) respectively, with no statistically
significance difference. Martínez-Ramos
[13] presented a meta-analysis comparing laparoscopy to open surgery, predominantly in
AGC. The study demonstrated no significant differences between the two groups in the
number of dissected lymph nodes (weighted mean difference, WMD −1.57, 95% confidence
interval −3.41 to 0.26, I-squared = 8.3). There studies suggested that LAG D2 radical surgery for AGC is feasible
and safe and the number of harvested lymph nodes is the same as in open surgery. We
found that skilled laparoscopic surgical technology and thorough palpation of anatomical
layers under laparoscopy is the key to lymph node dissection. The laparoscopic amplification
elaborately shows the finer structure of the vasculature, nerves and fascia, which
helps surgeons to seek a specific fascia space and facilitates lymph nodes dissection
in the vascular sheath. Furthermore, the ultrasonic scalpel is effective for cutting,
for hemostasis and for minimizing damage to the surrounding tissues, which is suitable
for vascular separation and lymph node dissection. The number of resected lymph nodes
in our study was enough for curability and to determine lymph node metastasis. Our
data show that the mean number of retrieved lymph nodes was not different between
the LAG and OG group. Furthermore, the mean number of removed lymph nodes in each
station was not significantly different with distal or total gastrectomy. For AGC
without invasion of serosa, laparoscopy-assisted D2 lymphadenetomy is able to achieve
the same effect on lymph node dissection as open surgery, regardless of the extent
of the gastrectomy. The surgical approach (laparoscopy or open) did not appear to
influence the lymph node yield.

To date, laparoscopic surgery for early gastric carcinoma has achieved favorable short-
and long-term efficacy
[6-8,24,25]. Although the efficacy of laparoscopic surgery for AGC is rarely reported, the results
also show it can achieve almost the same short- and long-term efficacy as open surgery.
Hur
[26] compared 26 cases of laparoscopic surgery and 25 cases of open surgery for treatment
of AGC. The 3-year survival rate in the laparoscopy and open surgery groups was 88.2%
and 77.2%respectively, with no statistical difference. A case–control study reported
by Shuang
[27] demonstrated the same survival curve for laparoscopy versus open surgery during the
same period and showed that laparoscopic surgery has similar long-term efficacy for
treatment of AGC. Our study also showed that the survival curves for the LAG and OG
groups were not significantly different (P > 0.05). LAG and OG have similar short survival times, but the long-term effect needs
to be followed-up.

In summary, if surgeons are proficient in laparoscopic surgical techniques and comply
with the principles of surgery, LAG D2 radical surgery can achieve similar, or even
better effects compared to open surgery, and can achieve a comparative short-term
clinical efficacy for treatment of AGC without serosal invasion. To establish laparoscopic
surgery as a standard treatment for AGC, multicenter randomized controlled trials
comparing the short- and long-term outcomes of laparoscopic versus open surgery are
necessary.

Competing interests

The authors declare they have no competing interests.

Authors' contributions

QYC, CMH and JXL conceived the study, analyzed the data, and drafted the manuscript;
CHZ helped revise the manuscript critically for important intellectual content; PL,
JWX, JBW and JL helped collect data and design the study. All authors read and approved
the final manuscript.